Separate pathways for cellular uptake of ferric and ferrous iron.

Article Details

Citation

Conrad ME, Umbreit JN, Moore EG, Hainsworth LN, Porubcin M, Simovich MJ, Nakada MT, Dolan K, Garrick MD

Separate pathways for cellular uptake of ferric and ferrous iron.

Am J Physiol Gastrointest Liver Physiol. 2000 Oct;279(4):G767-74. doi: 10.1152/ajpgi.2000.279.4.G767.

PubMed ID
11005764 [ View in PubMed
]
Abstract

Separate pathways for transport of nontransferrin ferric and ferrous iron into tissue cultured cells were demonstrated. Neither the ferric nor ferrous pathway was shared with either zinc or copper. Manganese shared the ferrous pathway but had no effect on cellular uptake of ferric iron. We postulate that ferric iron was transported into cells via beta(3)-integrin and mobilferrin (IMP), whereas ferrous iron uptake was facilitated by divalent metal transporter-1 (DMT-1; Nramp-2). These conclusions were documented by competitive inhibition studies, utilization of a beta(3)-integrin antibody that blocked uptake of ferric but not ferrous iron, development of an anti-DMT-1 antibody that blocked ferrous iron and manganese uptake but not ferric iron, transfection of DMT-1 DNA into tissue culture cells that showed enhanced uptake of ferrous iron and manganese but neither ferric iron nor zinc, hepatic metal concentrations in mk mice showing decreased iron and manganese but not zinc or copper, and data showing that the addition of reducing agents to tissue culture media altered iron binding to proteins of the IMP and DMT-1 pathways. Although these experiments show ferric and ferrous iron can enter cells via different pathways, they do not indicate which pathway is dominant in humans.

DrugBank Data that Cites this Article

Drugs
Drug Carriers
DrugCarrierKindOrganismPharmacological ActionActions
Ferric cationCalreticulinProteinHumans
Unknown
Binder
Details
Ferric cationIntegrin beta-3ProteinHumans
Unknown
Binder
Details
Tetraferric tricitrate decahydrateCalreticulinProteinHumans
Unknown
Binder
Details
Tetraferric tricitrate decahydrateIntegrin beta-3ProteinHumans
Unknown
Binder
Details